On January 8, 2024 HighField Biopharmaceuticals, a clinical stage immuno-oncology company using lipid-based therapeutics to treat cancer, reported that it has completed its Phase 1a study of HF1K16 (Press release, HighField Biopharmaceuticals, JAN 8, 2024, View Source [SID1234639137]). Treating patients having multiple tumor types, the data demonstrated that the drug, administered as a single agent, is well-tolerated with only one dose-limiting toxicity (DLT) at the highest dose level. HF1K16 is a drug encapsulated immune modulating liposome containing all-trans retinoic acid.

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"We were especially encouraged by the outcome being correlated to the treatment duration, with the drug being tolerated for extended periods," said Dr. Yuhong Xu, CEO of HighField. "One glioma patient experienced complete remission after 10 months of treatment, remained on the treatment for two years and is cancer free. Another patient, with grade IV duodenal cancer, maintained stable disease for more than 5 months."

A total of 14 patients, suffering from a variety of refractory metastatic solid tumors such as gliomas and stomach, colorectal, liver, lung and ovarian cancers, were treated in China with HF1K16 at escalating doses beginning in 2022.

Overall, the disease control rate for the patients is about 35% with a median overall survival of 8.5 months. The maximum survival period has exceeded 24 months and five patients have survived more than 10 months.

"Given the disease state of the patients in the study, a monotherapy outcome of 35% disease control rate is impressive," said Dr. Xu. "Moreover, we found significant changes in the patients’ myeloid cell and T cell profiling after treatment. Because it shows a new mechanism and excellent safety profile, our next step is to explore HF1K16 in combination with chemotherapy and other immuno-oncology therapies."

HF1K16 is a unique liposome construct of ATRA, a small molecule metabolite of vitamin A. It is administered by infusion, travels through the blood stream and infiltrates the tumor microenvironment. ATRA is released and initiates the maturation of myeloid-derived suppressor cells (MDSCs).

MDSCs are immature myeloid cells which have not differentiated. ATRA promotes the maturation and differentiation of MDSCs into functional cells, such as dendritic cells, which then summon T cells to attack the cancer.

For more information on the Phase 1a open label trial see NCT05388487 at clinicaltrials.gov.

On January 8, 2024 Schrödinger, Inc. (Nasdaq: SDGR), Schrödinger (Nasdaq: SDGR), whose physics-based computational platform is transforming the way therapeutics and materials are discovered, reported an update on its progress across the business and announced its development and operational goals for 2024 (Press release, Schrodinger, JAN 8, 2024, View Source [SID1234639136]).

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Today Schrödinger announced an expanded, three-year, software agreement with Eli Lilly and Company. The three-year agreement builds on the collaboration established in 2022. The agreement provides Lilly with large-scale access to Schrödinger’s full suite of technologies to enable and accelerate all stages of drug discovery, from target enablement and assessment of target druggability to hit discovery and lead optimization activities through development candidate identification. Schrödinger will provide advanced support to ensure full integration and optimization of the platform across Lilly’s research sites.

"We made important progress across the business in 2023, working with Lilly and other companies to enable more discovery programs at scale, expanding the capabilities of our platform, and increasing our focus on our proprietary pipeline,1 which now includes two clinical-stage development candidates," stated Ramy Farid, Ph.D., chief executive officer at Schrödinger. "We see continued opportunities this year to grow our software business, progress a third development candidate into the clinic, and advance our ongoing clinical studies to enable data readouts from our first two patient trials in late 2024 or 2025."

"Our conviction about our own programs is increasing. We continue to be selective about entering new collaborations, and we will allocate more of our drug discovery resources to our proprietary pipeline this year," stated Geoff Porges, MBBS, chief financial officer of Schrödinger. "We expect our drug discovery revenue in 2024 to be similar to or lower than 2022,2 reflecting these changes in our strategic priorities and the strategic decisions by certain partners to return programs in 2023. We believe our increased focus on our proprietary pipeline creates multiple paths for generating meaningful value in the coming years."

2023 Achievements

Today Schrödinger highlighted several 2023 achievements:

Proprietary Pipeline

Presented initial results from the healthy volunteer study of SGR-1505, its MALT1 inhibitor
Advanced the Phase 1 study of SGR-1505 in patients with advanced B-cell malignancies, including expanding the study at additional sites in the U.S. and Europe
Received FDA orphan drug designation for SGR-1505 in mantle cell lymphoma
Received IND clearance for SGR-2921, its CDC7 inhibitor, and initiated a Phase 1 study in patients with AML and MDS
Advanced SGR-3515, its Wee1/Myt1 inhibitor, to development candidate status and initiated IND-enabling activities
Presented preclinical data for SGR-1505 and SGR-2921 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and for the NLRP3 program at the Inflammasome Therapeutics Summit
Progressed newly disclosed discovery programs, including EGFRC797S, PRMT5-MTA and NLRP3 discovery programs
Platform

Released new and major improvements to existing technologies, including enabling the optimization of certain key ADMET properties, the first full release of technology to predict antibody affinity as a function of pH, software to more accurately predict small molecule pKa values, and a computational approach to identify brain penetrant molecules
Published 21 peer-reviewed articles in life sciences and materials science journals
Business

Appointed Margaret Dugan, M.D., as chief medical officer to lead clinical development and regulatory strategy for Schrödinger’s proprietary pipeline
Strengthened balance sheet with $147.3M in cash distributions from Nimbus’s sale of its TYK2 inhibitor to Takeda
Renewed and expanded battery research agreement with Gates Ventures for second three-year term
Published inaugural corporate sustainability report
2024 Development and Operational Goals

Today Schrödinger outlined the following development and operational goals for 2024:

Development Goals

Advance the Phase 1 study of SGR-1505 in advanced B cell malignancies to enable initial data release in late 2024 or 2025
Advance the Phase 1 study of SGR-2921 in patients with AML/MDS to enable initial data release in late 2024 or 2025
Submit the IND application for SGR-3515 in the first half of 2024 and initiate a Phase 1 study in 2024
Advance the discovery-stage proprietary pipeline to enable an additional IND submission in 2025
Present additional data from proprietary programs in one or more peer-reviewed forums
Progress platform capabilities associated with biologics
Publish research from the Gates battery research project building on existing publications
Operational Goals

Drive continued scale up and adoption of Schrödinger’s software platform across life sciences and materials science industries
Generate positive returns from strategic investments of Schrödinger’s technology, expertise and capital
Schrödinger will report its fourth quarter and full-year financial results and provide 2024 financial guidance on Wednesday, February 28, 2024, after the financial markets close. The company will host a conference call and webcast at 4:30 p.m. ET.

On January 8, 2024 Eikon Therapeutics, Inc., a pioneering biotechnology company that leverages advanced engineering to enhance drug discovery and development, reported that the company will provide an overview of clinical and preclinical progress in a presentation at the 42nd Annual J.P. Morgan Healthcare Conference on Monday, January 8th at 9:00 AM Pacific Time (Press release, Eikon Therapeutics, JAN 8, 2024, View Source [SID1234639135]).

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"Eikon has made enormous progress in the development of advanced imaging tools that aid the discovery of important new therapeutics. Our clinical pipeline now includes an immunomodulatory agent, active both by itself and in combination with PD-(L)1 inhibitors, which is entering global Phase 2 studies, as well as a highly selective PARP1 inhibitor for which a Phase 1 program is now enrolling appropriate patients," said Roger M. Perlmutter, M.D., Ph.D., CEO and Board Chair of Eikon Therapeutics. "Beyond these important clinical studies, we have a set of promising development candidates that are expected to advance into the clinic over the next 12 to 24 months. Our progress showcases the integrated clinical development capabilities of Eikon’s team and demonstrates that our proprietary instruments can identify novel chemical matter with especially desirable pharmaceutical properties. These achievements offer the promise of improved treatment outcomes in cancer patients, and in patients afflicted with intractable inflammatory or neurodegenerative conditions."

Key updates:

EIK1001 Advances to Phase 2: Eikon’s most advanced candidate, EIK1001, a systemically administered TLR 7 and 8 co-agonist, has received Investigational New Drug Application (IND) clearance from the U.S. Food and Drug Administration (FDA) and has proceeded into the first of several planned Phase 2 trials focused, in this case, on patients with advanced lung cancer when administered in combination with standard-of-care pembrolizumab plus chemotherapy. The Phase 2 investigation of EIK1001 is supported by compelling data from a Phase 1 trial of over 300 patients, demonstrating its promise both as a standalone agent and in rational combinations with PD-(L)1 inhibitors.
EIK1003 Now Enrolling Patients: Eikon’s selective PARP1 inhibitor, EIK1003, has entered a Phase 1/2 clinical trial at multiple U.S. sites assessing safety and tolerability in adult patients that have received at least one prior PARP inhibitor treatment for specific solid tumors expressing selected deleterious genetic mutations. International sites will join the trial early in 2024. Preclinical studies of EIK1003 (formerly IMP1734) have shown remarkable biochemical and cellular selectivity, positioning it as a potential therapeutic option with less hematologic toxicity when compared to existing PARP1/2 inhibitors. This program is led by Eikon with its collaboration partner, Impact Therapeutics, which is responsible for trial oversight in greater China.
IND-enabling Studies Begin for Brain-Penetrant PARP1 Inhibitor, IMP17307: Collaborating with Impact Therapeutics, Eikon has initiated IND-enabling studies for a brain-penetrant PARP1 candidate and is planning for a Phase 1 clinical trial in 2025.
Discovery Pipeline Progress: Using its proprietary platform, Eikon is conducting lead optimization for several programs including those targeting the androgen receptor and its clinically relevant variants, as well as several targeting key proteins in the DNA damage repair pathway including Werner (WRN). The company anticipates nominating a new clinical candidate in early 2024.
Eikon Systems Business Unit Established: Eikon has developed a suite of instruments that permits detailed, automated characterization of protein motion in living cells. Since most proteins function by interacting with other cellular structures (including other proteins), analysis of the dynamic behavior of individual protein molecules yields information regarding the function and regulation of biologic systems. These tools are increasingly sought after by academic investigators through Eikon’s Technology Access Program. The company expects that instruments from Eikon Systems will help to catalyze the use of protein motion measurements routinely as a means of elucidating biological processes.
An archived recording of Eikon’s presentation at the J.P. Morgan Healthcare Conference can be accessed at: www.EikonTx.com/#news.

On January 8, 2024 Johnson & Johnson (NYSE: JNJ) reported that it has entered into a definitive agreement to acquire Ambrx Biopharma, Inc., or Ambrx (NASDAQ: AMAM), a clinical-stage biopharmaceutical company with a proprietary synthetic biology technology platform to design and develop next-generation antibody drug conjugates (ADCs), in an all-cash merger transaction for a total equity value of approximately $2.0 billion, or $1.9 billion net of estimated cash acquired (Press release, Johnson & Johnson, JAN 8, 2024, View Source [SID1234639134]).

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Ambrx is advancing a focused portfolio of clinical and preclinical programs designed to optimize efficacy and safety of its candidate therapeutics in multiple cancer indications, including ARX517, its proprietary ADC targeting PSMA for metastatic castration-resistant prostate cancer (mCRPC); ARX788, its proprietary ADC targeting human epidermal growth factor receptor 2 (HER2) for metastatic HER2+ breast cancer; and ARX305, its proprietary ADC targeting CD-70 for renal cell carcinoma.

"Ambrx’s ADC technology offers unique advantages in the conjugation of stable antibodies and cytotoxic linker payloads, which results in engineered ADCs that effectively kill cancer cells and limit toxicities," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson Innovative Medicine. "The results seen to date with ARX517 in mCRPC are promising and represent a potential first- and best-in-class targeted therapy for the treatment of this aggressive disease. In addition, Ambrx’s pipeline and ADC platform present exciting future opportunities to deliver enhanced, precision biologics as we look to transform the treatment of cancer and improve patients’ lives."

The planned acquisition presents a distinct opportunity for Johnson & Johnson to design, develop and commercialize targeted oncology therapeutics. Ambrx’s proprietary ADC technology incorporates the advantages of highly specific targeting monoclonal antibodies securely linked to a potent chemotherapeutic payload to achieve targeted and efficient elimination of cancer cells without the prevalent side-effects typically associated with chemotherapy. Building on a legacy of innovation in oncology and in prostate cancer, J&J scientists intend to work with Ambrx researchers, accelerating the Phase 1/2 APEX-01 study (NCT04662580) of ARX517 in advanced prostate cancer, while progressing a pipeline of novel ADC product candidates.

"With a median overall survival of less than two years and novel hormonal therapies moving earlier in the disease, significant unmet need remains in the treatment of mCRPC," said Margaret Yu, M.D., Prostate Cancer Disease Area Leader, Johnson & Johnson Innovative Medicine. "We see a unique opportunity to harness the potential of this innovative ADC platform, and with our deep understanding of prostate cancer, deliver a targeted PSMA therapeutic for addressing the growing needs of the more than 185,000 patients living with metastatic castration-resistant disease today1."

Ambrx was spun out of The Scripps Research Institute in 2003. The company pioneered the expanded genetic code technology platform for incorporation of synthetic amino acid (SAA) into proteins at any selected site using industry standard cell lines. SAAs allow engineered precision biologics with site-specific, homogenous and stable conjugation, overcoming limitations of traditional conjugation technologies.

About the Merger Agreement

Under the terms of the transaction, which was approved by the Johnson & Johnson Board of Directors, Johnson & Johnson (the Company) will acquire all of the outstanding shares of Ambrx’s common stock for $28.00 per share in cash through a merger of Ambrx with a subsidiary of the Company. The closing of the transaction is expected to occur in the first half of 2024, subject to receipt of Ambrx shareholder approval, as well as clearance under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions. The approximately $1.9 billion estimated net value of the transaction is based on Ambrx’s estimated fully diluted shares outstanding, less estimated net cash at the time of closing. Following completion of the transaction, Ambrx’s common stock will no longer be listed for trading on the NASDAQ Global Select Market.

The accounting treatment as a business combination or asset acquisition will be determined on or before the expected close of the transaction.

On January 8, 2024 Simcha Therapeutics ("Simcha"), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, reported that it has entered into a license and option agreement with Janssen Biotech, Inc. ("Janssen"), a Johnson & Johnson company, where Janssen will work to armor select CAR T-based cell therapy candidates with Simcha’s novel proprietary decoy-resistant IL-18 (DR-18) (Press release, Simcha Therapeutics, JAN 8, 2024, View Source [SID1234639133]). The agreement was facilitated by Johnson & Johnson Innovation.

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Under the terms of the agreement, Janssen will develop, manufacture, and commercialize DR-18 armored cell therapies for a set number of programs. In exchange, Simcha will receive an undisclosed upfront fee, potential option exercise fees and development and commercialization milestone payments.

"Interest in developing IL-18 therapeutic approaches for cancer has continued to increase in recent years, tying back to findings published by our scientific founder that reinvigorated therapeutic interest in this cytokine. Armoring CAR T cells to secrete IL-18 is one of the most exciting areas of research, and we are proud to move the research forward with Janssen," said Sanuj Ravindran, M.D., chief executive officer of Simcha. "We will continue to expand our focus on IL-18 and the range of modalities that have potential to significantly improve outcomes for cancer patients, including through our internal development programs and additional strategic partnerships in the future."